Treatment of temporomandibular joint internal derangement using MESNA injection

Introduction The development of temporomandibular disorders specifically emphasizes the biochemical changes occurring in the synovial fluid at different stages of temporomandibular joint disease. Research has indicated that inflammation may be a primary reason behind the pain and dysfunction in temporomandibular joint diseases. Since its clearance several years ago, MESNA (sodium 2-mercaptoethanesulfonate) has been used in various formulations as a mucolytic drug in the respiratory domain. It operates by disrupting the disulfide bonds present between polypeptide chains within mucus. MESNA exhibits minimal tissue distribution, with the material being swiftly and thoroughly eliminated via the kidneys. Objectives To assess the efficacy of injecting MESNA directly into the Temporomandibular Joint to treat internal derangement. Materials and methods A randomized clinical trial was conducted on sixty patients who exhibited non-responsiveness to conventional treatment and were diagnosed with TMJ anterior disc displacement with reduction. The patients were chosen from the outpatient clinic of the Oral and Maxillofacial Surgery Department at Tanta University Faculty of Dentistry. Two equal groups of patients were randomly assigned to each other. Group I (Mesna group) received intra-articular injection with MESNA solution. Group II (Standard group) received arthrocentesis with lactated ringer solution followed by injection of Hyaluronic Acid (HA). The data was gathered by functional examinations such as maximum interincisal opening (MIO) and clicking. A Visual Analogue Scale (VAS) assessed pain severity before and after treatments. Results Both MESNA and HA showed significant improvement up to six months of the follow-up compared to preoperative status, as evidenced by better mouth opening, lateral excursion, lower clicking, and reduced pain score in patients with TMDs. MESNA showed significant improvement during follow-up compared to HA. Conclusion Compared to HA, MESNA showed a more noticeable improvement during the follow-up period. Supplementary Information The online version contains supplementary material available at 10.1186/s12903-024-04615-w.


Introduction
The Temporomandibular joint (TMJ) is among the most intricate and complicated load-bearing joints within the human body.With its ellipsoid configuration, the TMJ forms a bicondylar articulation involving the synovial joints on the left and right sides.The TMJ is unique in its extensive structural complexity, consisting of a fibrous capsule, synovial membrane, a disk, fluid, and robust adjacent ligaments [1].The TMJ, essential to dental occlusion and the neuromuscular system, emerges as one of the most intricate joints within the human body [2].
Temporomandibular Disorders (TMD) have a multifaceted origin involving various factors, each contributing to initiating, perpetuating, and exacerbating TMD symptoms.The authors stress the importance of quickly identifying putative etiological components and evaluating each one's relative contribution.Ignorance of etiological variables can lead to treatment failures because effective management requires addressing the underlying causes.Treatment strategies may be less effective if the underlying causes persist [3][4][5][6].This proactive approach aims to impede the progression of untreated TMD cases, thereby preventing adverse outcomes.Neglected cases may result in a less favorable prognosis, including heightened pain, psychological distress, physical impairment, and limitations in mandibular movement [7].
Ten to fifteen% of adults suffer from TMD, according to epidemiological research, yet only 5% of them seek therapy.
The incidence of TMD peaks between the ages of 20 and 40, with women being twice as likely as men to experience it.Additionally, TMD imposes a significant financial burden.Symptoms of TMD can vary from mild discomfort to severe, debilitating pain, frequently accompanied by restrictions in jaw function [8].
Pain is the most prevalent symptom, frequently affecting the preauricular region and the chewing muscles.A restricted range of movement of the jaw is often reported by patients, combined with TMJ noises that are characterized by "popping, " "clicking, " "grating, " or "crepitus." Patients commonly present with a range of complaints, including earache, headache, jaw ache, facial pain, palpable muscle tenderness, restricted mouth opening, asymmetrical jaw movements, audible joint sounds, and muscle discomfort [9].Furthermore, nonpainful enlargement of masticatory muscles and abnormal teeth wear, frequently linked to oral parafunctional habits such as tooth grinding and jaw clenching, may manifest as associated issues [10].
Other signs and symptoms of TMD include Myofascial Pain Dysfunction Syndrome (MPDS) is marked by alterations in the stomatognathic system, encompassing pain, irregularities in jaw movement, and muscle spasms.Peripheral sensory neurons become hyperexcited, initiating an induction reaction in motor neurons, leading to spasms in the masticatory muscles.Prolonged muscle spasms give rise to muscular pain and irregular motion of the mandible.Effectively managing pain is crucial as it plays a central role in inducing and sustaining muscle spasms.While symptomatic treatment approaches may offer relief, addressing the underlying causes becomes imperative after symptom elimination [11].
"Joint dysfunction associated with an abnormal disc position and damage to the internal structures of the joint" is a standard definition of internal derangement [4]."Internal derangement" typically describes a localized mechanical issue that interferes with the joint's articular disk and condyle's natural alignment [12].According to Wilkes staging, TMJ intrinsic derangement can occur in four stages: displacement of the disc with reduction, Disc displacement that is reduced and occasionally locked, Disc displacement without reduction with mouth opening limitation, Disc displacement without reduction, without mouth opening limitation [3][4][5][6].
Dolwick, Farrar, and others have classified internal derangements into different severity categories [13][14][15].An audible click that may be heard throughout the opening and closing motions of the disk indicates a decreasing derangement and represents the disc returning to its usual place.A characteristic click usually occurs at 15-20 mm of opening, and a reciprocal click occurs at 10-15 mm of closure in cases with this condition.Meniscus reduction can induce a centralization of the mandible during maximal opening and a shift to the affected side.; this is frequently accompanied by possible joint and accompanying muscle pain.Conversely, a nonreducing derangement, often termed a "closed lock, " occurs when the jaw opens only 20-30 mm without detecting joint sounds.Arthrograms reveal a meniscus that is anteriorly displaced and unable to revert to its original position during maximal opening.Limited maximal opening, simultaneous discomfort, and unilateral jaw displacement towards the affected side during opening are often associated with this disorder [16].Although the precise etiology of internal derangements is unknown, yawning, overextension during dental treatment, the removal of a third molar, intubation anesthesia, or trauma are some of the factors that might induce mandibular hyperextension [13].
In terms of etiology, symptoms related to both the muscles and TM joint in Myofascial Pain Dysfunction Syndrome (MPDS) have primarily been associated with occlusion.The severe compression of posterior teeth's periodontal ligaments (PDLs) by occlusal surface friction and extended disclusion time causes muscle hyperfunction and ischemia, which sets off muscle spasms.As a result, this leads to muscle fatigue, which contributes to impaired mandibular movements, ultimately leading to their deterioration [11].An association that often exists between muscle spasms and extended disclusion time is occlusal surface friction [17], which applies tension to the mechanoreceptors located in the periodontal ligament of the posterior teeth.Consequently, muscle hyperfunction and ischemia ensue, resulting in fatigued muscles and consequent restrictions in mandibular motion [17].The reduction in Mandibular movements may occur more quickly if occlusion deteriorates.Crowns, bridges, and fillings are examples of interventions that may exacerbate occlusal degeneration.Additionally, and frequently without the patient's knowledge, Ligament laxity can influence how the joint components within the glenoid fossa move.
The primary goal in treating TMDs is to alleviate or reduce discomfort., mitigate joint sounds, and restore normal TMJ function.Various treatment modalities are utilized for this purpose, including soft diets, pharmacotherapy, inter-occlusal splints, intra-articular injections, physical therapy, arthrocentesis, hyaluronic acid (HA) joint injection, botulinum toxin (BTX) type A injection or open joint surgery [8].
Hyaluronic acid (HA) is a high-molecular-weight hydrophilic linear polyanionic polymer.It is made up of just glucuronic acid and N-acetylglucosamine repeating disaccharide units.HA has been recognized as a critical component in the fluid that lubricates joints and the surrounding tissue.Research has revealed that HA can reduce joint pain by lowering levels of inflammatory mediators.Intraarticular treatment of HA has been shown in multiple studies to provide long-lasting positive effects, with a half-life of around 13 h [18].HA assumes a distinctive structural function within articular cartilage.Multiple proteoglycans are attached to HA via link proteins, resulting in the development of vast proteoglycan aggregates [19].Collagen mesh fibers wrap the aggregate, constituting the primary content of the cartilage matrix.As a result, water can permeate, transforming cartilage into a flexible tissue resistant to regular joint pressure.HA is also the predominant macromolecular ingredient in synovial fluid, contributing to its viscoelastic qualities essential for joint lubrication.It also has a role in stabilizing joints and may enhance the supply of nutrients to the avascular surfaces within the joint [20].
Sodium-2-mercaptoethanesulfonate (MESNA) represents the sodium derivative of the 2-thiosulfonate anion, functioning as a coenzyme in the methanogenesis process of anaerobic archaebacteria.Its broad applications in medicine are attributed to its protective, antioxidant, and mucolytic properties.As a mucolytic agent, MESNA operates by breaking disulfide bonds within mucous polypeptide chains.Recently, there has been a growing interest in MESNA within neurotologic surgery, which shows promise as a potent chemical dissector.MESNA exhibits minimal tissue distribution and is wholly and rapidly eliminated by the kidneys [21].When MESNA is delivered locally, it does two functions: it lyses fibrosis branches and acts as an agent that removes or neutralizes free radicals., removing free radicals.The cumulative effect of these actions may contribute to nerve decompression and the elimination of fibrous tissues, resulting in substantial pain reductions and functional benefits [21].
Because of its capacity to scavenge radicals, MESNA is commonly used to prevent hemorrhagic cystitis after chemotherapy with alkylating drugs [23].In 1998 MESNA was patented for its application in dissecting pathological tissue from healthy tissue, particularly in local adhesions.Numerous experimental investigations have been undertaken to evaluate the effectiveness and tolerability of the substance in question [22,23]., by demonstrating an effect on collagen fibers.Recent human trials have evaluated the drug's ability to facilitate surgical dissections in a variety of contexts, including revision surgeries and primary procedures such as the Surgical excision of uterine fibroids or abnormalities in the lining of the uterus.MESNA has been used in the surgical treatment of cholesteatoma within the field of otorhinolaryngology.More precisely, the dura mater and facial nerve are among the neurological components to which the cholesteatoma matrix frequently adheres tenaciously in these instances.In addition, MESNA has been utilized in procedures involving neuromas, meningiomas, and cranium base tumors, with no reports of local complications [24].The utilization of MESNA topically during revision lumbar surgery has been found to accelerate the surgical process of dissecting peridural fibrosis and reduce the incidence of postoperative complications [26].
This study aimed to assess the effectiveness and safety of injecting MESNA directly into the temporomandibular joint (TMJ) to treat internal derangement.

Sample size calculation
Using GPower version 3.1.9.2 [24].Based on a prior investigation to assess the safety and effectiveness of MESNA (sodium 2-mercapto-ethane-sulfonate) injection into the epidural space in the failed back surgery syndrome, the minimal sample size was determined [21].The sample size was computed to identify the difference in VAS for pain assessment relying on previous study by Carassiti and colleagues (2018) [21].It was determined that the minimum necessary sample size was 25 patients per group (number of groups = 2), using a power of 80% and a significance level of 5% [25,26].The sample size was expanded to 30 patients per group after accounting for a 20% dropout rate [27].This prospective randomised controlled trial was performed at the Oral Maxillofacial Department of the Faculty of Dentistry at Tanta University.The study was registered on clinicaltrials.gov(ID: NCT05882604) at 22/5/2023.The recruitment of participants, however, commenced prior to the official registration of the study protocol.The study started in April 2023 and finished in April 2024.

Patient eligibility criteria
Seventy-eight patients were assessed for eligibility; fifteen did not meet the eligibility criteria, and three declined to participate in the research.Sixty patients were randomly allocated into two equal groups, the MESNA Group and the Standard Group (30 patients each) using permuted block technique for randomization (with variable block size).Random allocation was implemented using Online Randomization table generator (Fig. 1).The study is open-labelled (no-blinding was done).

Inclusion criteria
Adult patients aged 19-48 with good oral hygiene and no gender bias.The study targeted participants with TMJ dysfunction who had not undergone surgery, were in Wilkes stages II, III, or IV, and did not respond to conservative therapy after three months.

Exclusion criteria
Inflammatory or connective tissue disorder; Previous occurrence of autoimmune disease; Previous occurrence of neurological diseases.

Pre-surgical phase Diagnosis by clinical and radiological means
Patients suffering from TMJ internal derangement disease were diagnosed using a combination of clinical examination and radiographic imaging, including panoramic X-ray and Magnetic Resonance Imaging (MRI) conducted with the jaw in both closed and open positions to assess disc placement and translation.

Preoperative evaluation
The main complaint was documented.The history encompasses demographic data, the initiation and advancement of symptoms, a record of limited or Fig. 1 CONSORT flow diagram disruptive mouth opening, bruxism or grinding behaviors, and any previous treatment.The patient judged pain severity and location during forced mouth opening using a Visual Analogue Scale (VAS) with a range of 0 to 10, indicating jaw dysfunction and joint pain.
Clinical examination includes measuring and recording the maximum mouth openness (MMO) and the extent of sideways and forward movements of the jaw.What is the nature of the limitation in jaw mobility?Are the discomfort and mechanical elements responsible for this condition?Is the condition permanent or sporadic?Joint noises, such as clicks and crepitus, can be categorized into three classifications: none, early, or late, based on a clinical examination.

Preoperative therapy
All patients with internal deranagement received conservative treatment as their first option.The preauricular region's skin surface was sterilized using a povidone-iodine solution.On the canthus-tragus line, two places were identified: One located 10 millimeters in front and 2 millimeters below the tragus, and the other located 20 millimeters in front and 8 millimeters below the tragus.A solution of Levonordefrin at a concentration of 1:20000 is administered by injection into the joint cavity.To give auriculotemporal anesthesia in conjunction with 2% Mepivacaine HCL.

Surgical phase Arthrocentesis procedure
After preauricular injection of local anasthesia to block the auriculotemporal nerve [28], Two 20-gauge needles were inserted for entry and exit locations.An arthrocentesis was conducted to clean the upper joint area using 100 ml of lactated Ringer's solution to extract the catabolites from the synovial fluid.The procedure commenced with the infusion of 2 ml of lactated ringer fluid to enlarge the capsule then utilizing 80 ml of the same liquid for cleansing purposes.Following the arthrocentesis procedure, in the MESNA group, 2 ml of MESNA was administered into the affected joints, while the HA group received 2 ml of HA (Orthovisc) injections.After the needles were removed, the injection sites were bandaged with gauze bandages.(Fig. 2)

The post-surgical stage Postoperative evaluation
After undergoing treatment, the patient was re-evaluated at 1, 3, 6, and 1 year to determine the condition of their temporomandibular joint (TMJ).Clinical assessments of the patient revealed the subsequent findings (Fig. 2): I. Assess self-pain and jaw function with a VAS (0-10 scale).Patients utilize this scale to estimate their pain levels and jaw dysfunction; the results are compared to the amount of pain before surgery.According to the VAS, patients were asked about the following characteristics of their pain and dysfunction: II.To calculate mean lateral movement, add the distance in millimeters from the midline of the upper and lower jaws, then divide by two.III.Protrusive movement refers to the maximum forward movement between the labial and lingual surfaces of the maxillary and mandibular central incisors.IV.The patient's ability to repeatedly open and close their mouth was utilized to measure the quantity of TMJ sound, which was then recorded as absent or present (early, late, or neither).The evaluation was conducted using a scale with 0 at one end, indicating no noise, and 10 at the other, indicating severe noise, which might be the worst.V.A digital calibrator calibrated to millimeters was used to measure the maximum mouth opening (MMO) between the upper and lower incisors.VI.The patient's masticatory efficiency was tested on a scale, with a score of 0 indicating good and 10 indicating poor mastication, allowing them only to ingest liquid meals.

Primary outcome
Pain by Visual Analogue Scale.

Secondary outcomes
Mouth opening by digital caliper, Clicking by stethoscope in same periods, Lateral Excursion by digital caliper.

Times of measurement
Preoperative, one week, three months, six months and one year postoperatively.

Statistical analysis
The statistical analysis utilized IBM © , Armonk, NY, USA's SPSS v27.Shapiro-Wilks test was used to assess data distribution.Non-parametric statistics were adopted.Data were reported as the median and 25th to 75th percentile.Mann-Whitney and Friedmann's tests were used.A P value with two tails less than 0.05 was deemed statistically significant [29].

Results (data are presented as median [25th -75th percentile)
Biodata (Table 1) In the MESNA Group, the age ranged between 19 and 48 years, with a median of 28 years [four (13.33%) females and 26 (86.67%) males].In the Standard Group, it ranged from 24 to 44 years, with a median of 28.50 years [three (10.00%) females and 27 (90.00%)males].There was no statistical difference in age (p = .847)or sex (p = 1.000) between the two studied groups.

Clinical evaluation Pain (Visal Analogue Scale) (VAS) (Table 2; Fig. 3)
Preoperatively, there was no statistically significant difference in VAS score between the two studied groups (p = .549).One week, three months, six months, and one year postoperative, VAS score was statistically In the MESNA Group, the VAS decreased after one week postoperative, three months postoperatively, and six months postoperatively compared with preoperative (p < .001,p < .001,and p < .001,respectively).However, one year postoperatively, the VAS increased compared with one week postoperatively, three months postoperatively, and six months postoperatively (p < .001,p < .001,and p < .001,respectively).
In the Standard group, the VAS decreased after one week postoperative, three months postoperatively, and six months postoperatively compared with preoperative (p < .001,p < .001,and p < .001,respectively).However, one year postoperatively, the VAS increased compared with one week postoperatively and three months after surgery (p < .001and p < .001,respectively).
In the MESNA group, the within-group comparison revealed that the number of patients suffering clicking decreased significantly at one week, three months, and six months postoperatively compared with preoperative findings (p < .001,p < .001,p < .001,respectively).One year postoperatively, the number suffering from clicking statistically significantly returned to be statistically significantly higher compared with one week postoperatively, three months postoperatively, and six months postoperatively (p < .001,p < .001p < .001;respectively).
In the Standard group, the within-group comparison revealed that the number of patients suffering clicking decreased significantly at one week and three months, compared with preoperative findings (p = .016,p = .016,respectively).No significant change at 6 months postoperatively (p = .084).One year postoperatively, the number suffering from clicking statistically significantly returned to be statistically significantly higher compared with one week and three months postoperatively (p = .016,p = .016;respectively).

Mouth opening (Table 4; Fig. 4) Preoperative
In the MESNA Group, the Mouth Opening ranged from 11.22 to 21.00 mm, with a median of 17.25 mm, and in the Standard group the Mouth Opening ranged from 13.20 to 23.00, with a median of 18.25 mm.There was no statistically significant difference in the Mouth Opening between the two studied groups preoperatively.(p = .161)

One week postoperative
In the MESNA Group, the Mouth Opening ranged from 26.00 to 37.50, with a median of 28.00 mm, and In the Standard group, the Mouth Opening ranged from 18.00 to 33.00, with a median of 22.00 mm.There was a statistically significant higher difference in the Mouth Opening in the MESNA Group compared with the Standard group after one week postoperatively.(p < .001)

Three months postoperative
In the MESNA Group, the Mouth Opening ranged from 25.00 to 37.50 mm, with a median of 26.50 mm, and in the Standard group, the Mouth Opening ranged from 17.00 to 34.00, with a median of 21.00 mm.There was a statistically significant higher difference in the Mouth Opening in the MESNA Group compared with the Standard group after three months Postoperatively.(p < .001)Fig. 3 Box and whisker graph of VAS in the two standard groups, the thick line in the middle of the box represents the median, the box represents the inter-quartile range (from 25th to 75th percentiles), the whiskers represent the minimum and maximum

Six months postoperative
In the MESNA Group, the Mouth Opening ranged from 25.00 to 37.50, with a median of 27.00 mm, and in the Standard group, the Mouth Opening ranged from 17.00 to 34.00 mm, with a median of 21.00 mm.There was a statistically significant higher difference in the Mouth Opening in the MESNA Group compared with the Standard group after six months Postoperatively.(p < .001)

One year postoperative
In the MESNA Group, the Mouth Opening ranged from 16.00 to 29.00 mm with a median of 20.00 mm, and in the Standard group, the Mouth Opening ranged from 14.00 to 317.00 mm, with a median of 6.00 mm.There was a statistically significant higher difference in the Mouth Opening in the MESNA Group compared with the Standard group after one year Postoperatively.(p = .007)The pairwise comparison revealed a statistically significant decrease in Mouth Opening in the MESNA and Standard groups.(p < .001and p < .001,respectively) In the MESNA Group, the Mouth Opening statistically significantly increased after one week postoperative, three months postoperatively, and six months postoperatively compared with preoperative (p < .001,p < .001,and p < .001,respectively).However, one year postoperatively, the Mouth Opening statistically significantly decreased compared with one week postoperatively, three months postoperatively, and six months postoperatively (p < .001,p = .001,and p < .001,respectively).In the Standard group,  the Mouth Opening statistically significantly increased after one week postoperative, three months postoperatively, and six months postoperatively compared with preoperative (p < .001,p < .001,and p < .001,respectively).However, one year postoperatively, the Mouth Opening statistically signifyingly decreased compared with one week postoperatively and three months postoperatively (p < .001and p < .001,respectively).5; Fig. 5) Preoperative

Lateral excursion (Table
In the MESNA Group, the Lateral Excursion ranged from 2.00 to 4.76, with a median of 3.00 mm, and in the Standard group, it ranged from 2.80 to 5.00, with a median of 4.00 mm.There was a statistically significant higher Lateral Excursion in the Standard group compared with the MESNA Group preoperatively.(p = .001)

One week postoperative
In the MESNA Group, the Lateral Excursion ranged from 3.00 to 9.70, with a median of 7.00 mm, and in the Standard group, it ranged from 3.00 to 7.30, with a median of 5.00 mm.There was a statistically significant higher Lateral Excursion in the MESNA Group compared with the Standard group after one week postoperatively.(p < .001)

Three months postoperative
In the MESNA Group, the Lateral Excursion ranged from 5.00 to 9.70 mm, with a median of 7.00 mm, and in the Standard group, it ranged from 3.00 to 7.60 mm, with a median of 5.00 mm.There was a statistically significant higher Lateral Excursion in the MESNA Group compared with the Standard group after three months Postoperatively.(p < .001)Six Months Postoperative: In the MESNA Group, the Lateral Excursion ranged from 4.00 to 9.70 mm, with a median of 7.00 mm, and in the Standard group, it ranged from 3.50 to 6.00 mm, with a median of 4.10 mm.There was a statistically significant higher Lateral Excursion in the MESNA Group compared with the Standard group after six months Postoperatively.(p < .001)

One year postoperative
In the MESNA Group, the Lateral Excursion ranged from 3.00 to 6.00 mm, with a median of 5.00 mm, and in the Standard group, it ranged from 3.00 to 5.00 mm, with a median of 4.00 mm.There was a statistically significant higher Lateral Excursion in the MESNA Group compared with the Standard group after one year Postoperatively.(p = .012) The pairwise comparison revealed a statistically significant increase in Lateral Excursion in the MESNA and Standard groups.(p < .001and p < .001,respectively) In the MESNA Group, the Lateral Excursion statistically significantly increased after one week postoperative, three months postoperatively, and six months postoperatively compared with preoperative (p < .001,p < .001,and p < .001,respectively).However, one year postoperatively, the Lateral Excursion statistically significantly decreased compared with one week post postoperatively, three months postoperatively, and six months postoperatively (p < .001,p < .001,and p < .001,respectively).In the Standard group, the Lateral Excursion statistically significantly increased after one week postoperative, three months postoperatively, and six months postoperatively compared with preoperative (p < .001,p < .001,and p < .001,respectively).However, one year postoperatively, the Lateral Excursion statistically significantly decreased compared with one week postoperatively and three months postoperatively (p = .004and p = .002,respectively).

Discussion
Temporomandibular Joints (TMJ) Internal Derangement is a problematic condition described by an incorrect interaction between the disc and the mandibular condyle, mandibular fossa, and articular eminence.This disruption in the TMJ apparatus can cause pain, functional issues, and a reduction in quality of life [30].TMJ disorders are treated in a variety of ways, including conservative methods such as physical therapy, dental appliances, and medicine.These treatments reduce discomfort and restore jaw function before considering more intrusive options [31].
In recent years, MESNA (2-mercaptoethanesulfonate) injections have emerged as a viable therapy option in other medical contexts [21,22].Its use in this setting is based on its sulfhydryl groups, which are thought to disrupt disulfide connections within the thick collagenous network of the TMJ disc.Potentially, this action could decrease disc rigidity and enhance mobility [32].
As far as we know, this is the first study to evaluate the efficacy of MESNA injections in treating internal derangement of the TMJ.
The purpose of administering MESNA specifically into the temporomandibular joint (TMJ) space is to induce a biochemical change within the joint, which is intended to enhance disc mobility and alleviate symptoms related to internal derangement [33].Further investigation is required to ascertain the precise mechanism through which MESNA operates in the context of temporomandibular joint (TMJ) issues.
Arthrocentesis is utilized to mitigate negative pressure within the disc by implementing lavage and removing inflammatory mediators via rinsing [34,35].Some studies have documented a reduction in pain levels after arthrocentesis.The observed enhancement is the elimination of inflammatory mediators via arthrocentesis, resulting in a reduction in pain and an augmentation in the range of motion [36,37].
According to Nitzan et al. [35]., arthrocentesis significantly improved all patients' maximal mouth opening, lateral movement toward the unaffected side, and pain reduction.Yoda et al. [38] discovered that the clicking in nine out of the twelve joints improved following arthrocentesis.
Based on the results of the present investigation, the Standard group exhibited notable enhancements in mouth opening, clicking, lateral excursion, and pain levels one week, three months, and six months after the procedure compared to their preoperative measurements.This may help explain why HA's lubricating effect is exceptionally potent for the first three months.HIF prevents abrasion, maintains lubrication, or provides nourishment for the avascular disc and condylar cartilage [39].
A study by Alpaslan and Alpaslan [36].observed the effectiveness of arthrocentesis with and without a sodium hyaluronate injection.It revealed that patients with internal derangement benefited from reduced pain, more mouth opening, and enhanced function.They concluded that arthrocentesis with HA injection seems more effective than arthrocentesis alone.
Shakya et al. (2010) [40] performed a cross-sectional study to evaluate the effectiveness of sodium hyaluronate injections after arthrocentesis.Throughout a six-month follow-up, their results indicated that maximal mouth opening (MMO) improved by 92%, TMJ pain decreased by 84%, and clicking was eliminated in 80% of patients.
A study conducted by Bjørnland et al. (2007) [41] examined the efficacy of corticosteroid and HA injections in the temporomandibular joint (TMJ) following arthrocentesis.The research examined 40 cases and confirmed that both injections could alleviate pain and enhance function in individuals diagnosed with osteoarthritis.An exceptional reduction in TMJ discomfort was observed with these injections, particularly in comparison to myofascial and TMJ pain.In addition, it was discovered that HA injections effectively decreased the intensity of pain more so than corticosteroids; however, a transient period of discomfort ensued after the injections.
The current study's findings revealed that patients in the MESNA group significantly improved in mouth opening, lateral excursion, clicking, and pain.Comparing these improvements to preoperative measurements, they were noted one week, three months, and six months after surgery.
In otology, MESNA is used for the simple dissection of tissue layers during ear procedures, notably in situations of atelectatic ear and cholesteatoma, its use has grown in recent years.Multiple animal studies have demonstrated that MESNA has no detrimental effects on the cochlea and does not produce ototoxicity [42].
Recently, Carassiti et al. (2018) [21], assessed the safety and effectiveness of epidural space MESNA injection as a therapeutic intervention for failed back surgery syndrome (FBSS).Positive outcomes are suggested by the Initial findings of the study, which included the initial six Fig. 5 Box and whisker graph of Lateral Excursion (mm) in the two studied groups, the thick line in the middle of the box represents the median, the box represents the inter-quartile range (from 25th to 75th percentiles), the whiskers represent the minimum and maximum patients who were afflicted with Persistent and incapacitating pain as a result of FBSS.The results of this study revealed that all patients observed during the threemonth follow-up period experienced notable functional improvement, as measured by a reduction of over 20% in the Oswestry Disability Index (ODI), significant pain relief of more than 20%, and a reduction in opioid intake.As indicated by improvements in pain and the Oswestry Disability Index (ODI), MESNA may be a feasible alternative to conventional treatment based on the study's findings.Comparing the MESNA group to the Standard group, the present study revealed significant improvements in mouth opening, lateral excursion, clicking, and discomfort scores one week, three months, six months, and one year postoperatively.

Conclusion
Both HA and MESNA demonstrated significant improvements up to six months of follow-up compared to the preoperative status.This was evidenced by better mouth opening, lateral excursion, reduced clicking, and lower pain scores in patients with internal derangement.Additionally, MESNA showed significant reduction in pain intensity during the follow-up period compared to HA.

Limitations
The sample size was relatively small.The study was in a single center.The follow-up of patients was limited to a relatively short period.Further comparative studies will be valuable in confirming the results of MESNA as a new treatment for internal derangement of TMJ.

Fig. 4
Fig. 4 Box and whisker graph of Mouth opening (mm) in the two studied groups, the thick line in the middle of the box represents the median, the box represents the inter-quartile range (from 25th to 75th percentiles), the whiskers represent the minimum and maximum

Table 1
Demographic data of the studied groups df: degree of freedom NS: Statistically not significant (p ≥ .05)

Table 2
Visual Analogue Scale (VAS) at different times of measurements in the studied groups

Table 3
Clicking at different times of measurements in the studied groups * Statistically significant (p < .05)NA: Non-applicable statistical (due to exact match)

Table 4
Mouth Opening (mm) at different times of measurements in the studied groups

Table 5
Lateral excursion (mm) at different times of measurements in the studied groups